CANVAS Substudy Explores Biomarkers on CV and Kidney Outcomes

Canagliflozin may delay longitudinal rise in high-sensitivity cardiac troponin T (hs-cTnT) and suppression of tumorigenesis-2 (sST2) vs. placebo through 6 years. In addition, cardiovascular biomarkers alone and in combination may predict subsequent clinical outcomes, independent of and incremental to common clinical parameters, according to a post-hoc biomarker substudy of the CANVAS trial, published Jan. 31 in the Journal of the American College of Cardiology.

Muthiah Vaduganathan, MD, MPH, FACC, et al., aimed to determine whether hs-cTnT, soluble, sST2, and insulin-like growth factor binding protein 7 (IGFBP7) levels, either alone or in combination, may modify the treatment benefits of canagliflozin. The researchers evaluated the prognostic significance of baseline biomarker measurements, the long-term trajectory of each, and response to canagliflozin on key cardiovascular and kidney outcomes.

Results showed that among the 4,330 study participants, baseline hs-cTnT, sST2, and IGFBP7 were available in 3,503 (81%), 3,084 (71%), and 3,577 (83%). In total, 39% had elevated hs-cTnT ≥14 pg/mL, 6% had sST2 >35 ng/mL, and 49% had IGFBP7 >96.5 ng/mL. Of note, canagliflozin significantly slowed increases of hs-cTnT (P=0.027) and sST2 (P=0.033) through 6 years.

The authors also found that each biomarker was “significantly associated with cardiovascular and kidney outcomes, independent of clinical covariates.” Further, canagliflozin reduced heart failure and kidney events regardless of baseline biomarker concentration. Patients with hs-cTnT ≥14 ng/L and those with sST2 >35 ng/mL derived greater relative benefit for major adverse cardiovascular events (MACE).

In addition, a panel of all three biomarkers predicted each cardiac and kidney outcome evaluated; participants with an increasing number of abnormal circulating biomarkers appeared to have greater relative reductions in MACE from canagliflozin treatment.

In a related editorial comment, Justin B. Echouffo-Tcheugui, MD, PhD, and Elizabeth Selvin, PhD, MPH, write: “The findings from this study demonstrate the potential of using biomarkers for clinical risk stratification among high-risk individuals – the vast majority of CANVAS participants had a history of [cardiovascular disease]. There has been a paucity of multimarker studies among individuals with a high burden of conventional risk factors and/or existing [cardiovascular disease].”

They add that moving forward, “additional studies in multiethnic cohorts, preferably of individuals without known CVD, will extend these findings and help identify populations most likely to benefit from SGLT2i therapy.”

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Acute Heart Failure

Keywords: Kidney, Cardiology, Carcinogenesis, Hospitalization, Insulin-Like Growth Factor Binding Proteins, Risk Assessment, Risk Factors, Heart Failure, Cardiovascular Diseases, Prognosis, Canagliflozin, Troponin T

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